Sedation Research in Critically Ill Pediatric Patients: Proposals for Future Study Design From the Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research IV Workshop.

OBJECTIVES: Sedation and analgesia for infants and children requiring mechanical ventilation in the PICU is uniquely challenging due to the wide spectrum of ages, developmental stages, and pathophysiological processes encountered. Studies evaluating the safety and efficacy of sedative and analgesic management in pediatric patients have used heterogeneous methodologies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research (SCEPTER) IV hosted a series of multidisciplinary meetings to establish consensus statements for future clinical study design and implementation as a guide for investigators studying PICU sedation and analgesia. DESIGN: Twenty-five key elements framed as consensus statements were developed in five domains: study design, enrollment, protocol, outcomes and measurement instruments, and future directions. SETTING: A virtual meeting was held on March 2-3, 2022, followed by an in-person meeting in Washington, DC, on June 15-16, 2022. Subsequent iterative online meetings were held to achieve consensus. SUBJECTS: Fifty-one multidisciplinary, international participants from academia, industry, the U.S. Food and Drug Administration, and family members of PICU patients attended the virtual and in-person meetings. Participants were invited based on their background and experience. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Common themes throughout the SCEPTER IV consensus statements included using coordinated multidisciplinary and interprofessional teams to ensure culturally appropriate study design and diverse patient enrollment, obtaining input from PICU survivors and their families, engaging community members, and using developmentally appropriate and validated instruments for assessments of sedation, pain, iatrogenic withdrawal, and ICU delirium. CONCLUSIONS: These SCEPTER IV consensus statements are comprehensive and may assist investigators in the design, enrollment, implementation, and dissemination of studies involving sedation and analgesia of PICU patients requiring mechanical ventilation. Implementation may strengthen the rigor and reproducibility of research studies on PICU sedation and analgesia and facilitate the synthesis of evidence across studies to improve the safety and quality of care for PICU patients.

Tracheal Intubation by Advanced Practice Registered Nurses in Pediatric Critical Care: Retrospective Study From the National Emergency Airway for Children Registry (2015-2019).

OBJECTIVES: To describe tracheal intubation (TI) practice by Advanced Practice Registered Nurses (APRNs) in North American PICUs, including rates of TI-associated events (TIAEs) from 2015 to 2019. DESIGN/SETTING: Retrospective study using the National Emergency Airway Registry for Children with all TIs performed in PICU and pediatric cardiac ICU between January 2015 and December 2019. The primary outcome was first attempt TI success rate. Secondary outcomes were TIAEs, severe TIAEs, and hypoxemia. SUBJECTS: Critically ill children requiring TI in a PICU or pediatric cardiac ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 11,012 TIs, APRNs performed 1,626 (14.7%). Overall, TI by APRNs, compared with other clinicians, occurred less frequently in patients with known difficult airway (11.1% vs. 14.3%; p < 0.001), but more frequently in infants younger than 1 year old (55.9% vs. 44.4%; p < 0.0001), and in patients with cardiac disease (26.3% vs. 15.9%; p < 0.0001).There was lower odds of success in first attempt TI for APRNs vs. other clinicians (adjusted odds ratio, 0.70; 95% CI, 0.62-0.79). We failed to identify a difference in rates of TIAE, severe TIAE, and oxygen desaturation events for TIs by APRNs compared with other clinicians. The TI first attempt success rate improved with APRN experience (< 1 yr: 54.2%, 1-5 yr: 59.4%, 6-10 yr: 67.6%, > 10 yr: 63.1%; p = 0.021). CONCLUSIONS: TI performed by APRNs was associated with lower odds of first attempt success when compared with other ICU clinicians although there was no appreciable difference in procedural adverse events. There appears to be a positive relationship between experience and success rates. These data suggest there is an ongoing need for opportunities to build on TI competency with APRNs.

Ketamine Use in the Intubation of Critically Ill Children with Neurological Indications: A Multicenter Retrospective Analysis.

BACKGROUND: Ketamine has traditionally been avoided for tracheal intubations (TIs) in patients with acute neurological conditions. We evaluate its current usage pattern in these patients and any associated adverse events. METHODS: We conducted a retrospective observational cohort study of critically ill children undergoing TI for neurological indications in 53 international pediatric intensive care units and emergency departments. We screened all intubations from 2014 to 2020 entered into the multicenter National Emergency Airway Registry for Children (NEAR4KIDS) registry database. Patients were included if they were under the age of 18 years and underwent TI for a primary neurological indication. Usage patterns and reported periprocedural composite adverse outcomes (hypoxemia < 80%, hypotension/hypertension, cardiac arrest, and dysrhythmia) were noted. RESULTS: Of 21,562 TIs, 2,073 (9.6%) were performed for a primary neurological indication, including 190 for traumatic brain injury/trauma. Patients received ketamine in 495 TIs (23.9%), which increased from 10% in 2014 to 41% in 2020 (p < 0.001). Ketamine use was associated with a coindication of respiratory failure, difficult airway history, and use of vagolytic agents, apneic oxygenation, and video laryngoscopy. Composite adverse outcomes were reported in 289 (13.9%) Tis and were more common in the ketamine group (17.0% vs. 13.0%, p = 0.026). After adjusting for location, patient age and codiagnoses, the presence of respiratory failure and shock, difficult airway history, provider demographics, intubating device, and the use of apneic oxygenation, vagolytic agents, and neuromuscular blockade, ketamine use was not significantly associated with increased composite adverse outcomes (adjusted odds ratio 1.34, 95% confidence interval CI 0.99-1.81, p = 0.057). This paucity of association remained even when only neurotrauma intubations were considered (10.6% vs. 7.7%, p = 0.528). CONCLUSIONS: This retrospective cohort study did not demonstrate an association between procedural ketamine use and increased risk of peri-intubation hypoxemia and hemodynamic instability in patients intubated for neurological indications.

2022 Society of Critical Care Medicine Clinical Practice Guidelines on Prevention and Management of Pain, Agitation, Neuromuscular Blockade, and Delirium in Critically Ill Pediatric Patients With Consideration of the ICU Environment and Early Mobility.

RATIONALE: A guideline that both evaluates current practice and provides recommendations to address sedation, pain, and delirium management with regard for neuromuscular blockade and withdrawal is not currently available. OBJECTIVE: To develop comprehensive clinical practice guidelines for critically ill infants and children, with specific attention to seven domains of care including pain, sedation/agitation, iatrogenic withdrawal, neuromuscular blockade, delirium, PICU environment, and early mobility. DESIGN: The Society of Critical Care Medicine Pediatric Pain, Agitation, Neuromuscular Blockade, and Delirium in critically ill pediatric patients with consideration of the PICU Environment and Early Mobility Guideline Taskforce was comprised of 29 national experts who collaborated from 2009 to 2021 via teleconference and/or e-mail at least monthly for planning, literature review, and guideline development, revision, and approval. The full taskforce gathered annually in-person during the Society of Critical Care Medicine Congress for progress reports and further strategizing with the final face-to-face meeting occurring in February 2020. Throughout this process, the Society of Critical Care Medicine standard operating procedures Manual for Guidelines development was adhered to. METHODS: Taskforce content experts separated into subgroups addressing pain/analgesia, sedation, tolerance/iatrogenic withdrawal, neuromuscular blockade, delirium, PICU environment (family presence and sleep hygiene), and early mobility. Subgroups created descriptive and actionable Population, Intervention, Comparison, and Outcome questions. An experienced medical information specialist developed search strategies to identify relevant literature between January 1990 and January 2020. Subgroups reviewed literature, determined quality of evidence, and formulated recommendations classified as "strong" with "we recommend" or "conditional" with "we suggest." Good practice statements were used when indirect evidence supported benefit with no or minimal risk. Evidence gaps were noted. Initial recommendations were reviewed by each subgroup and revised as deemed necessary prior to being disseminated for voting by the full taskforce. Individuals who had an overt or potential conflict of interest abstained from relevant votes. Expert opinion alone was not used in substitution for a lack of evidence. RESULTS: The Pediatric Pain, Agitation, Neuromuscular Blockade, and Delirium in critically ill pediatric patients with consideration of the PICU Environment and Early Mobility taskforce issued 44 recommendations (14 strong and 30 conditional) and five good practice statements. CONCLUSIONS: The current guidelines represent a comprehensive list of practical clinical recommendations for the assessment, prevention, and management of key aspects for the comprehensive critical care of infants and children. Main areas of focus included 1) need for the routine monitoring of pain, agitation, withdrawal, and delirium using validated tools, 2) enhanced use of protocolized sedation and analgesia, and 3) recognition of the importance of nonpharmacologic interventions for enhancing patient comfort and comprehensive care provision.

The New Trainee Effect in Tracheal Intubation Procedural Safety Across PICUs in North America: A Report From National Emergency Airway Registry for Children.

OBJECTIVES: Tracheal intubation carries a high risk of adverse events. The current literature is unclear regarding the "New Trainee Effect" on tracheal intubation safety in the PICU. We evaluated the effect of the timing of the PICU fellow academic cycle on tracheal intubation associated events. We hypothesize 1) PICUs with pediatric critical care medicine fellowship programs have more adverse tracheal intubation associated events during the first quarter (July-September) of the academic year compared with the rest of the year and 2) tracheal intubation associated event rates and first attempt success performed by pediatric critical care medicine fellows improve through the 3-year clinical fellowship. DESIGN: Retrospective cohort study. SETTING: Thirty-seven North American PICUs participating in National Emergency Airway Registry for Children. PATIENTS: All patients who underwent tracheal intubations in the PICU from July 2013 to June 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The occurrence of any tracheal intubation associated events during the first quarter of the academic year (July-September) was compared with the rest in four different types of PICUs: PICUs with fellows and residents, PICUs with fellows only, PICUs with residents only, and PICUs without trainees. For the second hypothesis, tracheal intubations by critical care medicine fellows were categorized by training level and quarter for 3 years of fellowship (i.e., July-September of 1st yr pediatric critical care medicine fellowship = first quarter, October-December of 1st yr pediatric critical care medicine fellowship = second quarter, and April-June during 3rd year = 12th quarter). A total of 9,774 tracheal intubations were reported. Seven-thousand forty-seven tracheal intubations (72%) were from PICUs with fellows and residents, 525 (5%) with fellows only, 1,201 (12%) with residents only, and 1,001 (10%) with no trainees. There was no difference in the occurrence of tracheal intubation associated events in the first quarter versus the rest of the year (all PICUs: July-September 14.9% vs October-June 15.2%; p = 0.76). There was no difference between these two periods in each type of PICUs (all p ≥ 0.19). For tracheal intubations by critical care medicine fellows (n = 3,836), tracheal intubation associated events significantly decreased over the fellowship: second quarter odds ratio 0.64 (95% CI, 0.45-0.91), third quarter odds ratio 0.58 (95% CI, 0.42-0.82), and 12th quarter odds ratio 0.40 (95% CI, 0.24-0.67) using the first quarter as reference after adjusting for patient and device characteristics. First attempt success significantly improved during fellowship: second quarter odds ratio 1.39 (95% CI, 1.04-1.85), third quarter odds ratio 1.59 (95% CI, 1.20-2.09), and 12th quarter odds ratio 2.11 (95% CI, 1.42-3.14). CONCLUSIONS: The New Trainee Effect in tracheal intubation safety outcomes was not observed in various types of PICUs. There was a significant improvement in pediatric critical care medicine fellows' first attempt success and a significant decline in tracheal intubation associated event rates, indicating substantial skills acquisition throughout pediatric critical care medicine fellowship.

Evaluating Patient-Centered Outcomes in Clinical Trials of Procedural Sedation, Part 2 Safety: Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations.

The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, established by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks, a public-private partnership with the US Food and Drug Administration, convened a second meeting of sedation experts from a variety of clinical specialties and research backgrounds to develop recommendations for procedural sedation research. The previous meeting addressed efficacy and patient- and/or family-centered outcomes. This meeting addressed issues of safety, which was defined as "the avoidance of physical or psychological harm." A literature review identified 133 articles addressing safety measures in procedural sedation clinical trials. After basic reporting of vital signs, the most commonly measured safety parameter was oxygen saturation. Adverse events were inconsistently defined throughout the studies. Only 6 of the 133 studies used a previously validated measure of safety. The meeting identified methodological problems associated with measuring infrequent adverse events. With a consensus discussion, a set of core and supplemental measures were recommended to code for safety in future procedural clinical trials. When adopted, these measures should improve the integration of safety data across studies and facilitate comparisons in systematic reviews and meta-analyses.

Procedural sedation in children with autism spectrum disorders: A survey of current practice patterns of the society for pediatric sedation members.

BACKGROUND: Children with autism spectrum disorder are challenging to sedate because of communication, sensory, and behavioral challenges. AIMS: The aim of this survey was to determine how procedural sedation is provided to children with autism spectrum disorders and whether sedation programs have specialized protocols for procedural sedation of these children. METHODS: We surveyed physician Medical Directors of sedation programs who are members of the Society for Pediatric Sedation, asking about practice characteristics and resource utilization during procedural sedation of children with autism spectrum disorders. RESULTS: Of 58 directors, 47 (81%) responded. Of the programs surveyed, 53% were either a large university medical center and 40% were a freestanding children's hospital. Only (12/47, 25.5%) of the programs used an individualized autism coping plan. To accomplish procedural sedation in this study cohort, 36% of the programs used additional nurses, whereas a child life specialist was used in 55% of the programs surveyed. Only 28% of the centers allotted additional time to accommodate children with autism spectrum disorders. Distraction methods were used in 80% whereas restrains were used in 45% programs for were used most commonly for i.v. catheter placement. Propofol was the preferred agent for 70% of programs for imaging, while propofol + fentanyl was used by 66% of programs for painful procedures. Although 57% of directors reported that their program staff was extremely comfortable providing procedural sedation for children with autism spectrum disorder, 79% of the directors wanted more education about behavioral management strategies for procedural sedation of these children. CONCLUSION: Among the Society for Pediatric Sedation programs, significant institutional variation exists on the delivery of procedural sedation to children with autism spectrum disorders. A better understanding of resources required, standardization of behavioral management strategies and pharmacologic approaches, and protocol development may help optimize care to this vulnerable population.

Use of Thromboelastography to Predict Thrombotic Complications in Pediatric and Neonatal Extracorporeal Membranous Oxygenation.

The objectives of this study were to investigate the correlation between thromboelastography (TEG) and conventional measures of anticoagulation, and to determine optimum values for citrated kaolin TEG R time (TEG RCK) and anti-Xa activity that would minimize both bleeding and thrombotic complications in pediatric and neonatal patients requiring extracorporeal membranous oxygenation (ECMO). A retrospective chart review of patients requiring veno-venous (VV) and venoarterial (VA) ECMO was performed. Combined medical and cardiac ICU within a single-center, tertiary care, freestanding, children's hospital. Non-pregnant patients <18 years and >2 kilograms requiring VV or VA ECMO from July 2013 through July 2015. Anti-Xa (OR = 0.62, 95% CI 0.53-0.72, p < .001) and TEG RCK (OR = 1.19, 95% CI 1.07-1.34, p = .003) were the only independent predictors for a significant thrombotic event. Receiver operating characteristic curves and traditional epidemiological data (sensitivity, specificity, PPV, NPV) were used to determine optimal target Anti-Xa and TEG RCK values. No independent predictors for significant bleeding events were identified in this cohort. A anti-Xa activity of .25 IU/mL (sensitivity = 81%, specificity = 67%, PPV = 81%, NPV = 58%) and TEG RCK time of 17.85 minutes (sensitivity = 84%, specificity = 68%, PPV = 82%, NPV = 59%) were established as the optimal thresholds for preventing thrombotic events. Anti-Xa and TEG RCK were independent predictors of thrombosis in this cohort of pediatric and neonatal ECMO patients. Targeting an anti-Xa activity greater than .25 IU/mL and a TEG RCK greater than 17.85 minutes may minimize the risk of thrombosis in pediatric and neonatal ECMO patients. Future investigation should evaluate targets for anti-Xa and TEG RCK, which additionally minimize the risk of significant bleeding in this patient population.

Evaluating Patient-Centered Outcomes in Clinical Trials of Procedural Sedation, Part 1 Efficacy: Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations.

The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, established by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks public-private partnership with the US Food and Drug Administration, convened a meeting of sedation experts from a variety of clinical specialties and research backgrounds with the objective of developing recommendations for procedural sedation research. Four core outcome domains were recommended for consideration in sedation clinical trials: (1) safety, (2) efficacy, (3) patient-centered and/or family-centered outcomes, and (4) efficiency. This meeting identified core outcome measures within the efficacy and patient-centered and/or family-centered domains. Safety will be addressed in a subsequent meeting, and efficiency will not be addressed at this time. These measures encompass depth and levels of sedation, proceduralist and patient satisfaction, patient recall, and degree of pain experienced. Consistent use of the recommended outcome measures will facilitate the comprehensive reporting across sedation trials, along with meaningful comparisons among studies and interventions in systematic reviews and meta-analyses.

The impact of obesity on pediatric procedural sedation-related outcomes: results from the Pediatric Sedation Research Consortium.

OBJECTIVES: To evaluate the impact of obesity on adverse events and required interventions during pediatric procedural sedation. METHODS: The Pediatric Sedation Research Consortium database of prospectively collected procedural sedation encounters was queried to identify patients for whom body mass index (BMI) could be calculated. Obesity was defined as BMI ≥95th percentile for age and gender. Sedation-related outcomes, adverse events, and therapeutic interventions were compared between obese and nonobese patients. RESULTS: For analysis, 28,792 records were eligible. A total of 5,153 patients (17.9%) were obese; they were predominantly male and older and had a higher median American Society of Anesthesiologists Physical Status classification (P < 0.001). Total adverse events were more common in obese patients (odds ratio [OR] 1.49, 95% confidence interval [1.31, 1.70]). Respiratory events (airway obstruction OR 1.94 [1.54, 2.44], oxygen desaturation OR 1.99 [1.50, 2.63], secretions OR 1.48 [1.01, 2.15], laryngospasm OR 2.30 [1.30, 4.05]), inability to complete the associated procedure (OR 1.96 [1.16, 3.30]), and prolonged recovery (OR 2.66 [1.26, 5.59]) were increased in obese patients. Obese patients more frequently required airway intervention including repositioning, suctioning, jaw thrust, airway adjuncts, and bag-valve-mask ventilation. Multivariate regression analysis demonstrated obesity to be independently associated with minor and moderate but not major adverse events. CONCLUSIONS: Obesity is an independent risk factor for adverse respiratory events during procedural sedation and is associated with an increased frequency of airway interventions, suggesting that additional vigilance and expertise are required when sedating these patients.

Pretreatment with midazolam blunts the rise in intracranial pressure associated with ketamine sedation for lumbar puncture in children.

OBJECTIVE: Ketamine has a long history of use during pediatric procedural sedation. Concerns about raising intracranial pressure may limit use in certain situations. Whereas some data suggest that benzodiazepine coadministration may blunt this response, pediatric data during procedural sedation do not exist. We evaluated the effects of midazolam pretreatment on intracranial pressure during ketamine sedation in children. DESIGN: Prospective, randomized clinical study. SETTING: Outpatient Medical Observation unit at Kosair Children's Hospital. PATIENTS: A total of 25 oncology patients in whom sedated lumbar puncture was scheduled. INTERVENTIONS: Patients alternated between sedation in Group A (midazolam/ketamine prior to lumbar puncture) or Group B (ketamine only prior to lumbar puncture). Opening pressure, medication doses, sedation depth, and complications were recorded. A control group of non-ketamine-sedated patients (Group C) was added to differentiate drug vs. disease-specific opening pressure changes. Between-group differences were compared by linear mixed effects model or contingency table with p < 0.05 considered significant. MEASUREMENTS AND MAIN RESULTS: Twenty-five patients aged 82 ± 49 months were sedated 84 times. Thirty-five sedations were in Group A, 39 in Group B, and 10 in Group C. Mean (95% confidence interval) adjusted opening pressure in Group A (22.0 [12.3, 22.2] cm H2O) was lower than Group B (26.5 [24.0, 29.2] cm H2O, p = 0.013). Opening pressure in Group C (17.3 [12.3, 22.2] cm H2O) was lower than in Group B (p = 0.002) but not in Group A (p = 0.096). Ketamine doses were similar between Groups A and B (1.4 ± 0.6 mg/kg vs. 1.4 ± 0.4 mg/kg, p = NS). Mean midazolam pretreatment dose was 0.09 ± 0.02 mg/kg and did not correlate with measured opening pressure. Four patients, all in Group B, experienced significant emergence reactions. CONCLUSION: While pretreatment with midazolam is associated with a reduction in intracranial pressure compared with sedation with ketamine alone, ketamine-containing regimens are associated with higher opening pressures than non-ketamine-containing regimens.

Development, implementation, and initial participant feedback of a pediatric sedation provider course.

BACKGROUND: No standardized educational curriculum exists for pediatric sedation practitioners. We sought to describe the curriculum and implementation of a pediatric sedation provider course and assess learner satisfaction with the course curriculum. DESCRIPTION: The course content was determined by formulating a needs assessment using published sedation guidelines, reports of sedation related adverse events, and a survey of sedation practitioners. Students provided feedback regarding satisfaction with the course immediately following the course and 6 months later. EVALUATION: The course consisted of 5 didactic lectures, 1 small-group session, 6 simulation scenarios, a course syllabus, and a written examination. The course was conducted over 1 day at 3 different locations. Sixty-nine students completed the course and were uniformly satisfied with the course curriculum. CONCLUSIONS: A standardized pediatric sedation provider course was developed for sedation practitioners and consisted of a series of lectures and simulation scenarios. Overall satisfaction with the course was positive.

Associations With Severe Desaturation Events Among Children Receiving Noninvasive Respiratory Support at Time of Intubation.

BACKGROUND: Endotracheal intubation is a common procedure associated with adverse events, including severe desaturation. Many patients receive noninvasive respiratory support to reduce the need for intubation. There are minimal data about the association between noninvasive respiratory support and the risk of a severe desaturation event during intubation. We aim to differentiate patients based on the level of noninvasive respiratory support, analyze the severe desaturation event by groups, and identify modifiable risk factors. METHODS: Oral intubations, excluding tube exchanges or re-intubation after unplanned extubation, from October 2018 through July 2020, at the study site were reviewed. A severe desaturation event was defined as [Formula: see text] < 70% or a >15% decrease from baseline in cyanotic heart disease. We analyzed outcomes by 4 groups: room air/nasal cannula (≤0.5 L/kg/min), high-flow nasal cannula (HFNC) (0.5-2 L/kg/min), high HFNC (≥2 L/kg/min), and noninvasive ventilation (NIV). RESULTS: Of 243 subjects who were intubated, 31% were receiving room air/nasal cannula, 25% were receiving HFNC, 18% were receiving high HFNC, and 26% were receiving NIV. Twelve percent of all the subjects had a severe desaturation event. In a univariate analysis, the incidence of a severe desaturation event was similar among all levels of respiratory support (P = .14). A severe desaturation event was more likely in those subjects who were receiving [Formula: see text] ≥ 0.6 at the time of the decision to intubate (19.6%) versus [Formula: see text] < 0.6 (8.1%) (P = .02). The duration of noninvasive respiratory support was longer (5 vs 1 h; P = .02) among those with a severe desaturation event. In a regression analysis, when adjusting for ≥2 intubation attempts pre-intubation, NIV use was independently associated with increased odds of severe desaturation events (odds ratio 3.14, CI 1.08-10.5). CONCLUSIONS: Results of our study suggest that [Formula: see text] > 0.60, the duration of noninvasive respiratory support, and exposure to NIV before an intubation are risk factors of severe desaturation events during intubation.

A Multi-Center Evaluation of the Pharmacokinetics and Safety of Intravenous Ibuprofen in Infants 1-6 Months of Age.

BACKGROUND: Enteral ibuprofen was first approved as a prescription drug in 1974 for the US market. An intravenous (IV) ibuprofen formulation is approved for use in children older than 6 months of age, but there are limited studies specifically evaluating the pharmacokinetics and safety in children 1-6 months of age. AIMS: The primary purpose of this study was to evaluate the pharmacokinetics of IV ibuprofen in infants younger than 6 months of age. The secondary objective was to evaluate the safety of single and repeated doses of IV ibuprofen in infants younger than 6 months of age. METHODS: This was an industry-sponsored multi-center study. Institutional Review Board approval and informed parental consent were obtained prior to enrollment. Hospitalized neonates and infants younger than 6 months of age with fever or expected postoperative pain were eligible. Enrolled patients received 10 mg/kg of IV ibuprofen every 6 h, with up to four doses per day. Patients were randomized to two sparse sampling technique pharmacokinetic sample time groups. Group 1 samples were drawn at 0, 30 min, and 2 h, while group 2 samples were drawn at 0 min, 1, and 4 h after administration. RESULTS: A total of 24 children were enrolled in the study, with 15 male patients and 9 female patients. The median age of the cohort was 4.4 months (range 1.1-5.9 months), and the median weight was 5.9 kg (range 2.3-8.8 kg). The arithmetic mean and standard error for peak plasma ibuprofen concentration was 56.28 ± 2.77 µg/mL. Plasma levels declined rapidly with a mean elimination half-life of 1.30 h. Time to peak ibuprofen effect and concentration were similar when compared with older pediatric patients. Clearance and volume of distribution were also similar to those reported in older pediatric patients. No drug-related adverse events were reported. CONCLUSIONS: The pharmacokinetic and short-term safety profiles of IV ibuprofen in pediatric patients 1-6 months of age are comparable to those in children older than 6 months of age. TRIAL REGISTRATION: Clinicaltrials.gov Trial Registration number and date: NCT02583399-Registered July 2017.

Analysis of Viscoelastic Testing in Pediatric Patients Using the Pediatric Extracorporeal Membrane Oxygenation Outcomes Registry.

Use of viscoelastic tests (VETs), including thromboelastography (TEG) and rotational thromboelastometry (ROTEM), is increasing in the management of anticoagulation in extracorporeal membrane oxygenation (ECMO) patients. A retrospective review of data on 265 pediatric (<20 years old) ECMO patients who underwent VET and were submitted to the Pediatric ECMO Outcomes Registry (PEDECOR) was conducted to describe common coagulopathies in patients who underwent VET; associations between the VET parameters and traditional tests of coagulation; and comparisons in blood product usage in patients who underwent VET with those who did not. We calculated patient-level summary statistics and assessed differences between the groups using χ2 tests (categorical variables) and Kruskal-Wallis and Wilcoxon rank-sum tests (continuous variables). Viscoelastic test was utilized in 77% of patients in the analysis. Platelet dysfunction was the most common abnormality identified by TEG (30.8%) and ROTEM (9.7%). Bleeding patients who had VET performed received more cryoprecipitate transfusions than those who did not have VET (VET median = 9.7 ml/kg; interquartile range (IQR) = 4.3-22.0 ml/kg vs. no VET median = 5.1 ml/kg; IQR = 0-10.4 ml/kg; p = 0.0013). Given the growing use of VET in pediatric ECMO patients, further studies evaluating VET in managing complications as well as aiding in titration of anticoagulation therapy are needed.

Evaluation of cerebral oxygenation during procedural sedation in children using near infrared spectroscopy.

STUDY OBJECTIVE: We evaluate the utility of near infrared spectroscopy monitoring and its correlation to conventional respiratory monitors during changes in cardiorespiratory characteristics during pediatric procedural sedation. METHODS: In this prospective observational study of 100 children, cerebral oxygenation (rSO(2)), pulse oximetry (SpO(2)), and end-tidal carbon dioxide (etco(2)) were monitored continuously. Values were manually recorded at least every 3 minutes from baseline until 30 minutes after sedative administration, resulting in 1,515 triplicate (simultaneous near infrared spectroscopy/etco(2)/SpO(2)) measurements. Correlations between conventional monitoring characteristics (SpO(2) and etco(2)) and rSO(2) were determined, with focus during adverse cardiorespiratory events. RESULTS: Cerebral oxygenation remained normal in 1,483 of 1,515 measurements (97.9%). rSO(2) decreased significantly during 3 of 13 hypoxic events occurring in 13 patients and during 5 of 17 hypercarbic events occurring in 8 patients, with 15 measurements of greater than 20% decrease from baseline. Cerebral oxygenation increased transiently in 88% of children. During 31 cerebral desaturation recordings, 3 hypoxic recordings (9.3%, always in combination with hypercarbia) and 5 hypercarbic recordings (15.6%) were observed, whereas in 23 (74.2%), cardiorespiratory characteristics were unchanged. There was poor correlation between rSO(2) and both SpO(2) and etco(2), with correlation coefficients of 0.05 (95% confidence interval 0.04 to 0.07) and 0.01 (95% confidence interval -0.01 to 0.02), respectively. CONCLUSION: Cerebral oxygenation as measured by near infrared spectroscopy demonstrated few significant negative changes during pediatric procedural sedation. Transient cardiorespiratory events seldom altered rSO(2), with hypercarbia having a greater effect than hypoxemia. However, cerebral desaturations frequently occurred without associated cardiorespiratory changes.

Atrial fibrillation after taser exposure in a previously healthy adolescent.

We are reporting a previously healthy adolescent who developed atrial fibrillation after being tased. He has a structurally normal heart on echocardiogram, normal electrolyte level and thyroid function test results, and a urine toxicology screen positive for marijuana. The patient ultimately required external defibrillation to convert his cardiac rhythm to normal sinus rhythm and has had no recurrent arrhythmias since hospital discharge (approximately 1 year). This is the first reported case of atrial fibrillation developing after a Taser shot, occurring in an adolescent without other risk factors. This case illustrates the arrhythmogenic potential of a Taser in otherwise healthy young individuals, and further study of occurrence of Taser-induced arrhythmias is warranted.